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Bradley K. Wacker, Jennifer L. Perfater and Jeffrey M. Gidday Hypoxic preconditioning induces stroke tolerance in mice via a cascading HIF, sphingosine kinase, and CCL2 signaling pathway Journal of Neurochemistry 123

Article first published online: 1 NOV 2012 | DOI: 10.1111/jnc.12047

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Signaling the preconditioning genomic response

Preconditioning for stroke tolerance with hypoxia, cobalt, and FTY720 requires HIF activity and SphK2-generated S1P signaling via the S1P1 receptor. In turn, cross-talk/feedback between HIF and S1P signaling up-regulates CCL2 expression to induce this epigenetic response. The identification herein of multiple upstream mediators of ischemic tolerance provides several targets of translational relevance for preconditioning in humans.

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